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(Stroke. 1996;27:2211-2215.)
© 1996 American Heart Association, Inc.

Articles

-Thrombin Upregulates G_i3 in Human Vascular Endothelial Cells

S. Martin Shreeve, PhD; Marie A. Shatos, PhD Eric Thorin, PhD

the Totman Laboratory for Human Cerebrovascular Research (S.M.S., E.T.) and the Department of Biochemistry (M.A.S.), University of Vermont (Burlington).

Correspondence to S. Martin Shreeve, PhD, Totman Laboratory for Cerebrovascular Research, Department of Pharmacology, College of Medicine, Given Bldg, University of Vermont, Burlington, VT 05405. E-mail sshreeve@moose.uvm.edu.

Background and Purpose During thrombosis, -thrombin becomes sequestered by fibrin and the subendothelial basement membrane, and it is available to interact with the vasculature over prolonged periods. In this study, we investigated the long-term effect of -thrombin on G_i3 and G_s levels in human vascular endothelial cells (EC). Because obesity is associated with changes in receptor signaling in many animal models, we also explored the influence of this clinical risk factor.

Methods Primary cultures of human EC were exposed to -thrombin for 16 hours, and immunologically detectable G_i3 and G_s levels were measured.

Results -Thrombin (100 nmol/L) increased G_i3 levels in EC derived from the cerebral microvasculature and superficial temporal artery (4.2±1.2-fold and 2.8±0.32-fold, respectively) but had no significant effect on EC derived from omental artery (P>.6) or from the superficial temporal artery of obese (body mass index 28 kg/m²) patients (P>.4). The expression of G_s was unchanged in all cell types (P.1). Two other circulating peptides, vasoactive intestinal peptide and endothelin-1, failed to alter the expression of either G protein in EC from the cerebral microvasculature, further demonstrating the specificity of the -thrombin effect. However, thrombin receptor activating protein-14 mimicked the -thrombin response and increased G_i3 in EC derived from the cerebral microvasculature and superficial temporal artery.

Conclusions We conclude that -thrombin increases G_i3 expression in some EC through activation of its tethered liganded receptor. Obesity appears to suppress this action of -thrombin.

Key Words: endothelium • obesity • G-proteins • thrombin

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